Plasma galectin-3 is associated with decreased glomerular filtration rate in chronic HIV

Figures & data

Figure 1. The analysis of HIV causal effect on estimated glomerular filtration rate (eGFR), mediated by Galectin-3.

Table 1. Comparison of demographics and clinical parameters in PLWH and HIV-negative individuals.

Parameter^a	PLWH (n = 45)	HIV- (n = 58)	p-value
Age, years	51 [46, 56.5]	55 [47.5, 60.5]	0.125
Male, n (%)	42 (93.3%)	49 (84.5%)	0.165
Race
Caucasian/White, n (%)	28 (62.2%)	37 (63.8%)	0.885
African American/Black	1 (2.2%)	1 (1.7%)
Native American/Alaskan	1 (2.2%)	0 (0%)
Native Hawaiian/Pacific Islander^b	6 (13.3%)	6 (10.3%)
Asian	3 (6.7%)	5 (8.6%)
More than one race	6 (13.3%)	9 (15.5%)
Hispanic or Latino ethnicity, n (%)	7 (15.6%)	5 (8.6%)	0.277
History of hypertension, n (%)	15 (33.3%)	15 (25.9%)	0.408
History of diabetes mellitus, n (%)	3 (6.7%)	2 (3.4%)	0.451
History of smoking n, (%)	28 (62.2%)	32 (55.2%)	0.605
CD4^+ T cells, cells/µL	510.0 [424.0, 686.5]	—	—
Undetectable HIV RNA, n (%)	37 (82.2%)	—	—
Current use of tenofovir disoproxil fumarate n, (%)	33 (73.3%)	—	—
Serum creatinine, mg/dL	1.0 [0.9, 1.1]	1.0 [0.8, 1.1]	0.016*
eGFR CKD-EPI^c, mL/min/1.73 m²	86.8 [71.3, 91.8]	89.0 [78.6, 97.4]	0.071
Plasma Gal-3, ng/mL	6.4 [4.0, 8.5]	4.5 [2.3, 6.5]	0.020*

^a Data presented as median [Quartile 1, Quartile 3] for continuous variables and n (%) for proportions.

^b Includes any participant who indicated they are part-Native Hawaiian/Pacific Islander.

^c Estimated Glomerular Filtration Rate was calculated using the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) formula.

* p < 0.05.

Table 2. Correlation between galectin-3 and other immune parameters.^a

	Spearman’s rho	p-value
UACR	0.229	0.186
Serum cystatin C	0.059	0.701
CD4^+ T cells	−0.069	0.652
CD8^+ T cells	0.028	0.853
CD4/CD8 ratio	−0.043	0.781
Total monocyte count, cells/L	−0.316	0.034*
Classical monocytes, cells/L	−0.329	0.044*
Intermediate monocytes, cells/L	0.040	0.811
Non-classical monocytes, cells/L	−0.124	0.458
CRP	0.037	0.821
sE-Selectin	0.177	0.282
sICAM-1	0.138	0.401
IFN-γ	0.069	0.675
IL-1β	0.173	0.292
IL-6	0.005	0.978
IL-8	0.168	0.308
IL-10	−0.073	0.658
MCP-1	0.143	0.387
MMP-9	0.174	0.289
MPO	−0.101	0.540
SAA	−0.002	0.991
SAP	0.021	0.897
TNF-α	−0.013	0.939
tPAI-1	0.067	0.687
VCAM-1	−0.054	0.742
VEGF	−0.160	0.330

^a Number of participants with available data, n = 45.

* p < 0.05.

Abbreviations: Urine Albumin/Creatinine Ratio was calculated by: UACR (mg/g) = Urine Albumin (mg/dL)/Urine Creatinine (g/dL) ≈ Albumin excretion in mg/day; CRP, C-reactive protein; sE-selectin, soluble E-Selectin; SICAM, soluble intercellular adhesion molecule-1; IFN-γ, interferon-gamma; IL, interleukin; MCP-1, monocyte chemoattractant protein-1; MMP-9, matrix metalloproteinase-9; MPO, myeloperoxidase; SAA, serum amyloid A; SAP, serum amyloid P; TNF, tumor necrosis factor; tPAI-1, tissue plasminogen activator inhibitor-1; VCAM-1, vascular cell adhesion molecule-1; VEGF, vascular endothelial growth factor.

Table 3. Stepwise linear regression of factors associated with eGFR*.

		Unstandardized Coefficient (B)	Standardized β-coefficient	p-value	95% Confidence Interval for B
Model 1:	HIV status	−0.035	−0.193	0.051	−0.071	0.000
Model 2:	HIV status	−0.021	−0.114	0.227	−0.055	0.013
	Galectin-3	−0.010	−0.363	<0.001	−0.014	−0.005
Model 3:	HIV status	−0.030	−0.166	0.069	−0.063	0.002
	Galectin-3	−0.009	−0.334	<0.001	−0.013	−0.004
	Age	−0.004	−0.304	<0.001	−0.006	−0.002
Model 4:	HIV status	−0.029	−0.158	0.085	−0.062	0.004
	Galectin-3	−0.008	−0.324	<0.001	−0.013	−0.004
	Age	−0.003	−0.289	0.002	−0.006	−0.001
	Hypertension	−0.021	−0.103	0.247	−0.056	0.014
Model 5:	HIV status	−0.027	−0.149	0.101	−0.060	0.005
	Galectin-3	−0.008	−0.299	0.001	−0.013	−0.003
	Age	−0.003	−0.251	0.008	−0.005	−0.001
	Hypertension	−0.016	−0.079	0.383	−0.051	0.020
	Diabetes mellitus	−0.056	−0.132	0.170	−0.136	0.024
Model 6:	HIV status	−0.026	−0.145	0.112	−0.059	0.006
	Galectin-3	−0.008	−0.314	<0.001	−0.013	−0.003
	Age	−0.003	−0.230	0.018	−0.005	0.000
	Hypertension	−0.015	−0.075	0.404	−0.051	0.021
	Diabetes mellitus	−0.059	−0.140	0.150	−0.139	0.022
	Total monocyte count	−0.045	−0.086	0.339	−0.137	0.048

* Estimated glomerular filtration rate log₁₀ transformed.

Table 4. Results of the causal mediation analysis of HIV on estimated glomerular filtration rate, mediated by galectin-3.

	Estimate	95% CI Lower	95% CI Upper	p-value
Mediation effect	−0.0132	−0.0346	−0.0011	0.020
Direct Effect	−0.0288	−0.0553	0.0007	0.064
Total Effect	−0.0420	−0.0716	−0.0100	0.016
Prop. Mediated	0.3143	0.0274	0.9200	0.028

Data availability statement

The data that support the findings of this study are available from the corresponding author upon reasonable request.